Rectal Phenotype of Perianal Paget Disease: Rare Concomitant Phenomena

Aim: Classically, ‘Paget disease’ refers to a distinct histological pattern in breast carcinoma. Here, we review the clinicopathological features of anorectal adenocarcinoma with ‘pagetoid’ spread. Materials and Methods: Histological and immunohistochemical records for 11 cases of anorectal adenocarcinoma with pagetoid spread among 958 Japanese patients with primary rectal/anal carcinoma were reviewed. Results: Grossly, nine of 11 cases had areas of invasive carcinoma: Tubular adenocarcinoma in eight and neuroendocrine carcinoma in one. Pagetoid components were positive for cytokeratin 7 in eight cases, cytokeratin 20 and caudal type homeobox 2 in all 11 cases, and p63 in one case, but were negative for estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), gross cystic disease fluid protein-15, and GATA binding protein 3. Conclusion: The prevalence of perianal Paget disease in this series was 1.1%, with two cases of genuine perianal Paget disease with a rectal phenotype without invasive carcinoma. The rectal phenotype of perianal Paget disease may not be associated with HER2 overexpression.

Hybrid Carcinoma of the Parotid Gland: An Extremely Rare Three Cases with an Immunohistochemical Analysis and a Review of the Literature

Salivary hybrid carcinoma (HC) is defined as when two or more kinds of carcinoma exist at the same location in a single mass. We reestimated and examined three cases of salivary gland HC. Case 1 involved a 76-year-old male. Case 2 involved a 74-year-old female. Case 3 involved a 66-year-old male. Histologically, case 1 involved a combination of salivary duct carcinoma (SDC) and squamous cell carcinoma (SqCC). Immunohistochemically, the former was positive for gross cystic disease fluid protein (GCDFP)-15 and androgen receptor (AR). Case 2 involved a combination of SqCC and neuroendocrine carcinoma. Immunohistochemically the latter was positive for synaptophysin and neural cell adhesion molecule (NCAM). Case 3 involved a combination of SDC and epithelial–myoepithelial carcinoma (EMC). Immunohistochemically, the former was positive for GCDFP-15 and AR, whereas the inner cells of the latter were positive for cytokeratin 7, and the outer cells of the latter were positive for actin. Because of the transitional zone between SDC and EMC, it was speculated that high-grade SDC arose from low-grade EMC.

Altered Expression of miR-146a-5p and Bcl-2 in Oncocytic Carcinoma of the Breast: A Case Report

Background: Oncocytic carcinoma of the breast is extremely rare, and its molecular profile is poorly understood. The distinctive feature of oncocytic carcinoma of the breast is that the granular eosinophilic cytoplasm contains numerous mitochondria. Recently, microRNA-146a-5p has been identified as a contributor to carcinogenesis and as a mitochondria-related microRNA, which regulates the mitochondrial function affecting Bcl-2. Bcl-2 plays a role in mitochondrial apoptosis.Case presentation: We report the clinical features, histopathological features, and immunohistochemical and molecular findings of oncocytic carcinoma of the breast in a 76-year-old woman. Immunohistochemistry studies revealed that the tumor cells were positive for antimitochondrial antibody but negative for gross cystic disease fluid protein 15, which confirmed the diagnosis. For molecular profiling, expression of microRNA-146a-5p and Bcl-2 messenger RNA (mRNA), which are mitochondria-related small molecules, were evaluated using real-time reverse transcription polymerase chain reaction. We found that the expression of microRNA-146a-5p was significantly lower (p < 0.01) and that of Bcl-2 mRNA was significantly higher (p < 0.01) compared to the control group (with no specific type of breast cancer). Conclusions: The significant changes in the expression of microRNA-146a-5p and Bcl-2 are specific to oncocytic carcinoma of the breast. Therefore, we suggest that the use of microRNA-146a-5p to target Bcl-2 has a potential therapeutic effect on oncocytic carcinoma of the breast.

Hormone Receptor Expression Variations in Normal Breast Tissue: Preliminary Results of a Prospective Observational Study

Normal breast tissue undergoes great variations during a woman’s life as a consequence of the different hormonal stimulation. The purpose of the present study was to examine the hormonal receptor expression variations according to age, menstrual cycle, menopausal state and body mass index. To this purpose, 49 tissue samples of normal breast tissue, obtained during surgery performed for benign and malignant conditions, were immunostained with Estrogen (ER), Progesterone (PR) and Androgen receptors (AR). In addition, Ki67 and Gross Cystic Disease Fluid Protein were studied. The data obtained revealed a great variability of hormone receptor expression. ER and AR generally increased in older and post-menopausal women, while young women presented a higher proliferative rate, evaluated with Ki67. PR increase was observed in women with BMI higher than 25. The different hormonal receptor expression could favor the development of breast cancer.

The Added Value of SOX10 Immunohistochemistry to Other Breast Markers in Identifying Cytokeratin 5-Positive Triple Negative Breast Cancers as of Mammary Origin

<b><i>Aims:</i></b> Triple-negative breast cancer (TNBC) represents a specific group that lacks the expression of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor-2 and might also lack the expression other breast markers like GATA3, mammaglobin (MG), GCDFP15 (growth cystic disease fluid protein 15), and NYBR1; when this occurs, proving the breast origin of a metastasis is a challenging task. In the present study, we assessed the added value of SOX10 immunohistochemistry to known GATA3, MG, GCDFP15, and NY-BR-1 statuses in a series of CK5-positive primary TNBCs. <b><i>Methods:</i></b> Tissue microarrays were made from the formalin-fixed and paraffin-embedded blocks of 120 TNBCs, and 3-4-mm-thick sections were immunostained for SOX10. The cut-off for a positive reaction was at least 10% of tumor cells staining. <b><i>Results:</i></b> In our cohort, SOX10 positivity was seen in 82/119 cases, 61, 74, 76, and 82 all of which were GATA3, MG, GCDFP15, and NY-BR-1 negative, respectively. Of the SOX10 negative cases, 12 stained with at least another breast marker. Nevertheless, 25/119 (21%) cases remained negative with all markers assessed. <b><i>Discussion:</i></b> SOX10 proved to be the most commonly positive breast marker in our CK5 expressing TNBCs, but the other markers also had some additive value to SOX10.

A rare case of perianal apocrine adenocarcinoma

Apocrine adenocarcinoma is a rare primary cutaneous malignancy that arises from areas with high apocrine gland density, most frequently described in the axilla. There have only been three previously reported cases of apocrine adenocarcinoma in the anal/perianal region. A 72-year-old female presented for evaluation of a perianal lesion with persistent drainage that she had noticed for over a year. The patient proceeded with surgical excision of the perianal nodule. Diagnosis was made based on pathology demonstrating areas of mixed solid and trabecular areas with large nuclei and many prominent mitotic figures, which stained positive for periodic acid–Schiff–diastase, cytokeratin 7 and gross cystic disease fluid protein 15. We are reporting just the fourth such case of apocrine adenocarcinoma in the anal/perianal region. It is important to consider apocrine adenocarcinoma in our differential, because though apocrine adenocarcinoma has a benign clinical presentation, it can have a high incidence of lymph invasion on presentation.

High-Grade Endometrioid Carcinoma of the Endometrium With a GATA-3-Positive/PAX8-Negative Immunophenotype Metastatic to the Breast: A Potential Diagnostic Pitfall

This report describes clinicopathologic findings from the case of a patient with a breast mass that was ultimately diagnosed as a metastatic high-grade endometrioid carcinoma of endometrial origin. The breast lesion as well as the solid areas of the endometrial lesion displayed a similar immunoprofile: GATA3-positive; synaptophysin positive; negative for mammaglobin, gross cystic disease fluid protein-15, chromogranin, estrogen receptor, progesterone receptor, and HER2/neu; and intact expression of the DNA mismatch repair proteins MLH1, MSH2, MSH6, and PMS2. The breast lesion was negative for PAX-8, whereas the solid areas of the endometrial lesion showed focal weak positivity. A review of the literature on GATA-3 expression in endometrial carcinomas found a reported frequency of expression that ranged from 0% to 13% of cases, typically in a patchy, focal, and generally restricted pattern. However, GATA-3 may be diffusely expressed in high-grade endometrial carcinomas. Since the potential for PAX-8 expression to be lost in high-grade endometrioid carcinomas is well known, a GATA-3-positive/PAX8-negative immunoprofile may be encountered in high-grade endometrioid carcinomas of the endometrium, and this composite immunoprofile is a potential diagnostic pitfall when such a lesion is being evaluated in a breast metastasis.

Periampullary Metastases from Breast Cancer: A Case Report and Literature Review

We presented a metastatic breast cancer case who was afflicted with obstructive jaundice caused by an ampullary neoplasm. Since jaundice due to periampullary metastasis from breast cancer was a rare entity, a literature review of similar cases through the PubMed database was done. A total of 23 additional cases were found. Among these 24 cases, 5 presented with periampullary metastasis synchronously with the diagnosis of breast cancer, while 19 had metachronous periampullary metastasis with an interval ranging between 1.3 and 23 years from the initial diagnosis of breast cancer to the emergence of jaundice. It is intriguing to establish a differential diagnosis for common bile tract stricture prior to tissue biopsy, even with diagnostic workups including serum tumor markers, MRI plus MRCP, ERCP with intraductal brushing, and endoscopic ultrasound, in that the clinical, radiological, and endoscopic findings of metastatic lesions overlapped extensively with those found with primary periampullary malignancies. An immunohistochemical portfolio including cytokeratin7/20 (CK7/20), homeobox protein CDX2, human epidermal growth factor receptor 2 (HER2/neu), estrogen receptor alfa (ERα), progesterone receptor (PgR), mammaglobin, gross cystic disease fluid protein-15 (GCDFP-15), and transacting T-cell-specific transcription factor (GATA-3) was helpful for differential diagnosis among cases with ambiguous microscopic features.